The molecular mechanism involved in neuronal cell death associated with aging have not been fully explained. This project proposes to examine important sites which have been implicated in cell death: the voltage- dependent calcium channels of neuronal membranes and the intracellular calcium release channels in the endoplasmic reticulum. An understanding of the structure, function, and regulation of these critical sites in normal, aging models, and aged animals could provide the necessary background for successful therapeutic intervention. A second aspect of this project will be to develop antibodies, both monoclonal and polyclonal, which will allow the localization and visualization of calcium channels and important receptors. Chemical probes for calcium channels and for sites involved in IP3 action will also be developed. The antibodies and chemical probes will be a resource for other investigations in our overall program and will be invaluable to the scientific community in general.